PROJECT SUMMARY/ABSTRACT This F31 proposal details a comprehensive program of training and research activities, as well as mentorship that will provide the PI with the support, knowledge, and skills to launch a career as an independent investigator focused on understanding the psychobiological mechanisms of exercise and how this information can be applied to help clinical mental health populations, specifically Post-Traumatic Stress Disorder (PTSD). As demonstrated by the PI's educational background and graduate research training experience, he possesses the skills and experience needed to design and conduct physical activity research examining basic components of the endocannabinoid (eCB) system in humans and rodents. However, given the expansive neuromodulatory role the eCB system plays in stress-related disorders, the PI needs additional training and mentorship specific to examining the role of physical activity on additional components of the eCB system (i.e., cannabinoid receptor gene expression). Moreover, to most effectively examine stress-related disorders such as PTSD (which is a heterogeneous disorder), multiple units of analyses across the entire spectrum (from healthy controls to trauma-exposed adults with and without PTSD) need to be examined. This approach aligns with NIMH's Research Domain Criteria (RDoC), thus, the proposed training plan includes additional training in a translational experimental paradigm (i.e., threat anticipation task) that can be used to conduct research through a multidimensional approach consistent with RDoC. Specifically, the proposed research project will address the following aims: 1) to examine the psychobiological effects (i.e., eCB levels, cannabinoid receptor gene expression, negative & positive affect) of exercise in trauma-exposed adults with PTSD compared to trauma-exposed adults without PTSD (TE) and healthy controls (HC), and 2) to examine whether activating the eCB system via exercise vs quiet rest results in less anxiety and fear responses during a threat anticipation task in trauma-exposed adults with PTSD compared to TE adults and HC. The PI, along with co-sponsors Dr. Kelli Koltyn (UW ? Madison) and Dr. Cecilia Hillard (Medical College of Wisconsin) have designed a training plan that will help the PI to launch his career as an independent investigator capable of conducting research spanning several field (i.e., mental health, genetics, psychobiology). Specifically, the proposed training plan will allow the PI to: 1) enhance his knowledge on the eCB system and gene expression. Specifically, the PI will receive training on white blood cell extraction and processing, CB1 and CB2 receptor gene expression quantification via PCR techniques, and advanced biostatistical tests to analyze gene expression data; 2) expand his research program to incorporate a translational experimental paradigm and multi-dimensional approach to study the spectrum of PTSD consistent with the mission of NIMH's RDoC; and 3) pursue networking, career, and professional development opportunities to enhance the PI's ability to effectively disseminate his research and forge collaborations for future investigations. The overall objective of this training and research plan is to provide a translational platform to inform the development of novel intervention strategies for PTSD. If funded, the knowledge gained from the PI's research will potentially help the millions of individuals suffering from debilitating stress-related disorders, such as PTSD.